Self-Assembled Peptide Hydrogels for Delayed Macromolecule Release
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Solution Overview
Problem
Biopharmaceuticals, such as protein-based therapeutics, face challenges due to susceptibility to physical and chemical degradation, leading to short half-lives that limit their therapeutic efficacy, necessitating methods to increase their stability during storage and physiological conditions.
Innovation Solution
Development of hydrogels that incorporate anionic macromolecules with specific peptides, like MAX peptides, which form delayed-release systems capable of retaining therapeutic agents for extended periods by controlling diffusion coefficients and mesh sizes, ensuring prolonged release and enhanced stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If protein-based therapeutics are administered directly, then immediate therapeutic effect is achieved, but the half-life is short (2-100 minutes) due to physical and chemical degradation
Solution Approach 1:
The patent embeds protein-based therapeutics inside a hydrogel matrix formed by self-assembling peptides. The therapeutic agent is nested within the three-dimensional network structure of the hydrogel, providing physical protection against degradation while extending circulation half-life. The hydrogel acts as a protective container that releases the therapeutic agent in a controlled manner over time.
Solution Approach 2:
The patent creates a composite material system combining synthetic peptides (MAX peptides with specific sequences) and protein-based therapeutics. The peptide hydrogel matrix provides structural stability and controlled release properties, while the embedded therapeutic protein provides the biological activity. This composite structure resolves the contradiction by combining the stability of the synthetic peptide framework with the therapeutic function of the protein.
2Duration of action of moving object
If hydrogel mesh size is decreased to increase retention, then release rate is slowed, but diffusion of therapeutic agent is restricted
Solution Approach 1:
The patent utilizes changes in physiological parameters (pH, ionic strength, temperature) to dynamically control the hydrogel network structure and mesh size. At physiological pH 7.4 and 150 mM NaCl, the MAX peptides self-assemble into a hydrogel with optimal mesh size for retaining anionic macromolecules. The system automatically adjusts its retention properties in response to the physiological environment, providing delayed release without requiring manual intervention to change physical parameters.
3Duration of action of moving object
If electrostatic interactions are increased to enhance macromolecule retention, then release is delayed, but non-specific binding may increase
Solution Approach 1:
The patent employs peptides with specifically designed local charge distributions along their sequences. The MAX peptides contain strategically placed positively charged residues (lysine, arginine) at specific positions that create localized electrostatic interaction zones. This localized charge arrangement provides selective retention of anionic macromolecules through controlled electrostatic attraction while minimizing non-specific binding, as the positive charges are distributed in a pattern that favors interaction with target anionic therapeutics rather than random binding.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The hydrogel system effectively retains at least 25% of anionic macromolecules for 28 days, providing a slow and controlled release, thereby extending the therapeutic efficacy and stability of biopharmaceuticals.
Implementation Method 1
a peptide selected from the group consisting of SEQ ID NO:1 through SEQ ID NO:33
Implementation Method 2
a diffusion coefficient of the anionic macromolecule in the modified-release hydrogel
Implementation Method 3
shearing the hydrogel in the preceding paragraph under conditions sufficient to at least partially shear-thin the gel structure
Data Source
AI summary
A hydrogel for delayed release of an anionic macromolecule, wherein the hydrogel comprises the anionic macromolecule, 150 mM NaCl, and a peptide selected from the group consisting of SEQ ID NO:1 through SEQ ID NO:33 in an aqueous medium at a pH of 7.4; wherein the anionic macromolecule has an isoelectric point of at most 6.8; and wherein the hydrogel is capable of retaining at least 25% of the anionic macromolecule after 28-day extraction at 37° C. with a pH=7.4 BTP buffer containing 150 mM NaCl.